Current environmental concerns demand intensive research on conservation tillage for cotton production. Studies were conducted in 1994 and 1995 at Florence, SC, to evaluate weed and cotton response to various weed management systems in cotton with reduced tillage. Broadcast application of pendimethalin at 1.1 kg ai/ha and fluometuron at 2.2 kg ai/ha preemergence (PRE) followed by pyrithiobac at 0.07 kg ai/ha early postemergence (EPOST) was more effective than was a 38-cm band of these herbicides in controlling naturally occurring populations of sicklepod, Palmer amaranth, goosegrass, and southern crabgrass and in providing cotton yields equal to yields under weed-free conditions. With the 38-cm band of PRE and EPOST herbicides, two supplemental weed treatments at 3 and 7 wk after planting using glyphosate applied at 0.84 kg ae/ha POST with a hooded sprayer or a no-till cultivator was required to achieve acceptable weed control, but cotton yields were less than yields for the broadcast treatment alone. Glyphosate- or cultivation-only systems were generally ineffective in reducing weed interference and precluding cotton yield reductions. Optimum cotton production with reduced tillage can be achieved with broadcast application of PRE and EPOST herbicides but alternative methods offer promise for reducing costs and environmental effects and deserve additional study.